ID   IOD3_BOVIN              Reviewed;         301 AA.
AC   Q5I3B1;
DT   21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   14-MAY-2014, sequence version 3.
DT   03-AUG-2022, entry version 97.
DE   RecName: Full=Thyroxine 5-deiodinase;
DE            EC=1.21.99.3;
DE   AltName: Full=5DIII;
DE   AltName: Full=DIOIII;
DE   AltName: Full=Type 3 DI;
DE   AltName: Full=Type III iodothyronine deiodinase;
GN   Name=DIO3;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Hereford;
RX   PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA   Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA   Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA   Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT   "A whole-genome assembly of the domestic cow, Bos taurus.";
RL   Genome Biol. 10:R42.01-R42.10(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 19-301, AND TISSUE SPECIFICITY.
RC   TISSUE=Mammary epithelium;
RX   PubMed=15932406; DOI=10.1111/j.1365-2052.2005.01282.x;
RA   Connor E.E., Laiakis E.C., Fernandes V.M., Williams J.L., Capuco A.V.;
RT   "Molecular cloning, expression and radiation hybrid mapping of the bovine
RT   deiodinase type II (DIO2) and deiodinase type III (DIO3) genes.";
RL   Anim. Genet. 36:240-243(2005).
CC   -!- FUNCTION: Responsible for the deiodination of T4 (3,5,3',5'-
CC       tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3
CC       (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2
CC       are inactive metabolites. May play a role in preventing premature
CC       exposure of developing fetal tissues to adult levels of thyroid
CC       hormones. Can regulate circulating fetal thyroid hormone concentrations
CC       throughout gestation. Essential role for regulation of thyroid hormone
CC       inactivation during embryological development.
CC       {ECO:0000250|UniProtKB:P55073}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3,3',5'-triiodo-L-thyronine + A + H(+) + iodide = AH2 + L-
CC         thyroxine; Xref=Rhea:RHEA:18897, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16382, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:57261, ChEBI:CHEBI:58448; EC=1.21.99.3;
CC         Evidence={ECO:0000250|UniProtKB:P55073};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II
CC       membrane protein {ECO:0000250}. Endosome membrane {ECO:0000250};
CC       Single-pass type II membrane protein {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in mammary gland. Detected at
CC       lower levels in kidney, and at very low levels in the other tissues.
CC       {ECO:0000269|PubMed:15932406}.
CC   -!- SIMILARITY: Belongs to the iodothyronine deiodinase family.
CC       {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-24 is the initiator.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAW51124.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AAFC03027682; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AY858552; AAW51124.1; ALT_INIT; mRNA.
DR   RefSeq; NP_001010993.2; NM_001010993.3.
DR   STRING; 9913.ENSBTAP00000053144; -.
DR   PaxDb; Q5I3B1; -.
DR   PRIDE; Q5I3B1; -.
DR   Ensembl; ENSBTAT00000060550; ENSBTAP00000053144; ENSBTAG00000043578.
DR   GeneID; 494549; -.
DR   KEGG; bta:494549; -.
DR   CTD; 1735; -.
DR   VEuPathDB; HostDB:ENSBTAG00000043578; -.
DR   VGNC; VGNC:106711; DIO3.
DR   eggNOG; ENOG502S5FA; Eukaryota.
DR   GeneTree; ENSGT00940000154482; -.
DR   HOGENOM; CLU_1717459_0_0_1; -.
DR   InParanoid; Q5I3B1; -.
DR   OMA; FGSCSXP; -.
DR   OrthoDB; 977776at2759; -.
DR   Proteomes; UP000009136; Chromosome 21.
DR   Bgee; ENSBTAG00000043578; Expressed in placenta and 53 other tissues.
DR   GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004800; F:thyroxine 5'-deiodinase activity; IBA:GO_Central.
DR   GO; GO:0033798; F:thyroxine 5-deiodinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR   GO; GO:0097474; P:retinal cone cell apoptotic process; IEA:Ensembl.
DR   GO; GO:0046549; P:retinal cone cell development; IEA:Ensembl.
DR   GO; GO:0042404; P:thyroid hormone catabolic process; IEA:Ensembl.
DR   GO; GO:0042403; P:thyroid hormone metabolic process; IBA:GO_Central.
DR   InterPro; IPR000643; Iodothyronine_deiodinase.
DR   InterPro; IPR008261; Iodothyronine_deiodinase_AS.
DR   InterPro; IPR027252; Iodothyronine_deiodinase_I/III.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   PANTHER; PTHR11781; PTHR11781; 1.
DR   Pfam; PF00837; T4_deiodinase; 1.
DR   PIRSF; PIRSF001330; IOD; 1.
DR   PIRSF; PIRSF500144; IODI_III; 1.
DR   SUPFAM; SSF52833; SSF52833; 1.
DR   PROSITE; PS01205; T4_DEIODINASE; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Endosome; Membrane; Oxidoreductase; Reference proteome;
KW   Selenocysteine; Signal-anchor; Thyroid hormones biosynthesis;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..301
FT                   /note="Thyroxine 5-deiodinase"
FT                   /id="PRO_0000223867"
FT   TOPO_DOM        1..41
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        42..64
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        65..301
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        167
FT   NON_STD         167
FT                   /note="Selenocysteine"
SQ   SEQUENCE   301 AA;  33888 MW;  DDE86EBE1BBA7BE6 CRC64;
     MSRQAAPRWV VGEGRGTLGG AATMLRSLLL HSLRLCSQTA SCLVLFPRFL GTAFMLWLLD
     FLCIRKHLLG RRRRGQPEIE VELNSDGEEV PPDDPPVCVS DDNRLCTLAS LRAVWHGQKL
     DFFKQAHEGG PAPNSEVVLP DGFQNQHILD YARGNRPLVL NFGSCTUPPF MARMSAFQRL
     VTKYQRDVDF LIIYIEEAHP SDGWVTTDSP YSIPQHRSLE DRVSAARVLQ QGAPECALVL
     DTMTNSSSSA YGAYFERLYI IQSGTIMYQG GRGPDGYQVS EVRTWLERYD EQLHGPQPRR
     V